1. Field of the Invention
The present invention relates to carbazole derivatives and pharmaceutically acceptable salts thereof that act on the 5-HT7 receptor, methods for preparing the compounds, and pharmaceutical compositions containing the compounds as active ingredients.
2. Description of the Related Art
The neurotransmitter serotonin acts on 14 different serotonin receptors distributed in various organs and is responsible for various physiological phenomena. Of these, the 5-HT7 subtype is the most recently cloned serotonin receptor and is known to be abundantly distributed, particularly in the hypothalamus, thalamus, hippocampus, and cortex. The 5-HT7 receptor is also found in peripheral tissues, such as spleen, stomach, intestine, and coronary artery, as well as in the brain tissues. Such expression patterns indicate that the 5-HT7 receptor is involved in various functions and pathologies. Particularly, the 5-HT7 receptor is known to perform important functions in thermoregulation, circadian rhythm, learning and memory, sleep, and hippocampal signal transduction (Lowenberg, T. N. et al., Neuron (1993) 11: 449-458). The 5-HT7 receptor is also known to be implicated in neurological diseases, such as depression, migraine, anxiety, and pain, particularly inflammatory pain and neuropathic pain (see a) Schoeffter, P. et al. Br J Pharmacol (1996) 117: 993-994; b) Terron, J. A., Eur. J. Pharmacol (2002) 439: 1-11).
Numerous efforts have been made so far to develop 5-HT7 receptor antagonists and agonists. However, only a few selective 5-HT7 receptor antagonists were reported. For example, International Patent Publication Nos. WO 97/48681, WO 97/29097, WO 97/49695, WO 00/56712, and WO 03/48118 disclose sulfonamide-based antagonists. Further, International Patent Publication Nos. WO 99/24022 and WO 00/000472 disclose tetrahydroisoquinoline derivatives acting on the 5-HT7 receptor.
Despite the research, a need still exists to find compounds that have selective pharmacological activities against the 5-HT7 receptor, achieving excellent pharmacological effects against 5-HT7 receptor-mediated diseases and conditions and good pharmaceutical properties in terms of administration, dispersion, uptake, distribution, metabolism, and excretion.